The Agricultural Health Study (AHS) is a long-term prospective study of potential health effects associated with exposure to pesticides and other agricultural exposures. The study is a collaboration of the National Cancer Institute, the National Institute of Environmental Health Sciences, and the US Environmental Protection Agency. Farmers and their spouses and children are exposed to numerous potential hazards - many of which, such as pesticides, are relevant to the population at large. Farmers have been shown to be at increased risk for some cancers. Experimental and human studies of acute or high-dose exposures suggest that farmers may also be at increased risk of other adverse health effects. We are examining cancer incidence and other health endpoints in a prospective study of licensed pesticide applicators, spouses and children from North Carolina (NC) and Iowa (IA). Over a 3-year period, we enrolled more than 57,000 licensed applicators, representing 82% of eligible private pesticide applicators (largely farmers) in IA and NC and 43% of commercial applicators from Iowa. About 40% of the private applicators also completed a more detailed take-home questionnaire covering farming practices and health. Nearly 32,000 spouses of farmer applicators enrolled and 2/3 of these also provided data on reproductive health, including information on all children under age 21. Cancer incidence among the applicators, spouses, and children is determined through linkage with the population-based cancer registries in IA and NC. Follow-up computer-assisted telephone interviews are used to update exposure information and to collect information on changes in health status since enrollment in the study. Buccal-cell samples are being collected from participants in order to extract DNA for future analyses of gene and environment interactions. In addition, a dietary assessment (food frequency questionnaire) is self-completed and returned by mail. In-depth assessment of agricultural exposures is being made for a small sample of farmers and their families in order to validate the questionnaires and facilitate exposure classification. Both environmental and biological samples are being collected. Non-cancer outcomes of particular interest in this follow-up period include Parkinson's Disease, neurological symptoms related to pesticide use, autoimmune diseases, gestational diagetes, and premature ovarian failure in addition to cancer. Recent results from the Agricultural Health Study include: 1) Long-term exposure to pesticides is associated with increased reporting of neurological symptoms typically seen following acute exposures; 2) Death rates from most causes are substantially lower than expected in the cohort, possibly because of lower rates of smoking and other features of a healthy active lifestlye as well as a "health worker" effect; 3) Lack of strong evidence linking pesticides to breast cancer risk, although some individual pesticides may play a role; 4) Suggesetive links between paternal pesticide use and cancer risk in offspring, and increased risk for accident mortality among farm children; 5) Decreased fertility associated with parental use of solvents; 6) Confirmation of a link between fungicide use and risk of retinal degeneration in an analysis of data from spouses of licensed applicators. Other analysis focused on risk for specific cancers associated with use of individual pesticides, including glyphosate, carbofuran, and chlorpyrifos. Papers were also submitted on risk factors for rheumatoid arthritis, colon cancer, and timing of menopause. We continue to analyze cross-sesctional data on farm exposures and respiratory disease, including farmers lung and chronic bronchitis. A current analysis focuses on gestational diabetes and use of pesticides during pregnancy. We completed the first round of follow-up interviews and plans are underway for Phase III telephone interviews. Respiratory disease will be a new focus to follow up on findings based on cross-sectional enrollment data linking pesticides and other farm exposures to risk for asthma symptoms and and chronic lung diseases. A pilot study will be undertaken to assess the feasibility of measuring onset of puperty in offspring of pesticide applicators.